Center for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
J Am Chem Soc. 2023 Feb 15;145(6):3382-3393. doi: 10.1021/jacs.2c09853. Epub 2023 Feb 2.
The occurrence of modular peptide repeats in load-bearing (structural) proteins is common in nature, with distinctive peptide sequences that often remain conserved across different phylogenetic lineages. These highly conserved peptide sequences endow specific mechanical properties to the material, such as toughness or elasticity. Here, using bioinformatic tools and phylogenetic analysis, we have identified the GX8 peptide with the sequence GLYGGYGX (where X can be any residue) in a wide range of organisms. By simple mutation of the X residue, we demonstrate that GX8 can be self-assembled into various supramolecular structures, exhibiting vastly different physicochemical and viscoelastic properties, from liquid-like coacervate microdroplets to hydrogels to stiff solid materials. A combination of spectroscopic, electron microscopy, mechanical, and molecular dynamics studies is employed to obtain insights into molecular scale interactions driving self-assembly of GX8 peptides, underscoring that π-π stacking and hydrophobic interactions are the drivers of peptide self-assembly, whereas the X residue determines the extent of hydrogen bonding that regulates the macroscopic mechanical response. This study highlights the ability of single amino-acid polymorphism to tune the supramolecular assembly and bulk material properties of GX8 peptides, enabling us to cover a broad range of potential biomedical applications such as hydrogels for tissue engineering or coacervates for drug delivery.
在承重（结构）蛋白中，模块肽重复的出现是很常见的，其具有独特的肽序列，这些序列在不同的系统发育谱系中通常保持保守。这些高度保守的肽序列赋予材料特定的机械性能，例如韧性或弹性。在这里，我们使用生物信息学工具和系统发育分析，在广泛的生物体中鉴定出具有 GLYGGYGX 序列（其中 X 可以是任何残基）的 GX8 肽。通过简单地突变 X 残基，我们证明 GX8 可以自组装成各种超分子结构，表现出从液态凝聚微滴到水凝胶到硬固态材料等截然不同的物理化学和粘弹性性质。我们结合使用光谱学、电子显微镜、力学和分子动力学研究来深入了解驱动 GX8 肽自组装的分子尺度相互作用，强调了π-π堆积和疏水相互作用是肽自组装的驱动力，而 X 残基决定了调节宏观力学响应的氢键程度。这项研究强调了单个氨基酸多态性调节 GX8 肽的超分子组装和整体材料性质的能力，使我们能够涵盖广泛的潜在生物医学应用，例如用于组织工程的水凝胶或用于药物输送的凝聚物。
